title: The μ1 72-96 loop controls conformational transitions during reovirus cell entry.
abstract: The reovirus outer capsid protein μ1 forms a lattice surrounding the viral core. In the native state, μ1 determines the environmental stability of the viral capsid. Additionally, during cell entry, μ1 undergoes structural rearrangements that facilitate delivery of the viral cores across the membrane. To determine how the capsid-stabilizing functions of μ1 impinge on the capacity of μ1 to undergo conformational changes required for cell entry, we characterized viruses with mutations engineered at charged residues within the μ1 loop formed by residues 72 to 96 (72-96 loop). This loop is proposed to stabilize the capsid by mediating interactions between neighboring μ1 trimers and between trimers and the core. We found that mutations at Glu89 (E89) within this loop produced viruses with compromised efficiency for completing their replication cycle. ISVPs of E89 mutants converted to ISVP*s more readily than those of wild-type viruses. The E89 mutants yielded revertants with second-site substitutions within regions that mediate interaction between μ1 trimers at a site distinct from the 72-96 loop. These viruses also contained changes in regions that control interactions within μ1 trimers. Viruses containing these second-site changes displayed restored plaque phenotypes and were capable of undergoing ISVP-to-ISVP* conversion in a regulated manner. These findings highlight regions of μ1 that stabilize the reovirus capsid and demonstrate that an enhanced propensity to form ISVP*s in an unregulated manner compromises viral fitness.
authors.affiliation: Department of Biology, Indiana University, Bloomington, Indiana, USA.
authors.forename: Payel
authors.initials: P
authors.lastname: Sarkar
authors.forename: Pranav
authors.initials: P
authors.lastname: Danthi
mesh_terms: D000818:Animals; D002213:Capsid / Q000737:chemistry / Q000378:metabolism; D036022:Capsid Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003460:Crystallization; D012089:Mammalian orthoreovirus 3 / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D051379:Mice; D009154:Mutation; D011487:Protein Conformation; D012087:Reoviridae / Q000235:genetics / Q000502:physiology*; D012088:Reoviridae Infections / Q000821:virology*; D053586:Virus Internalization
chemical_list: D036022:Capsid Proteins; C055356:mu1 protein, Reovirus